The American Diabetes Association 73rd Scientific Sessions: Type 1 Diabetes
Type 2 drugs for type 1 diabetes show lots of promise at ADA.
by Adam Brown, Margaret Nguyen, and Alasdair Wilkins
Last month in Chicago at the ADA meeting, the most important scientific diabetes meeting of the year, updates for type 1 diabetes included lots of news on diabetes technology, exciting new data on Forxiga (an SGLT-2 inhibitor), and a 30-year update from DCCT/ EDIC, the landmark study on tight glycemic control. We also saw striking research being done to improve pumps and CGMs for people with type 1 or type 2.
A New Therapy for Type 1 Diabetes?
One key therapy study was of dapagliflozin, an SGLT-2 inhibitor. As a reminder, this type 2 diabetes drug class causes excess blood glucose to be excreted through urine. When trial participants took Forxiga over a 14-day period, their average daily blood glucose dropped by 10-20 mg/dl (relative to placebo) with less glycemic variability. Notably, they were able to take about 16-19% less total insulin than normal. A separate study of BI/Lilly's empagliflozin revealed similarly positive results over a much longer eight-week study period: a 16% decrease in insulin requirements, a 0.4% decline in A1c (from a starting baseline of 8%), and one-third of the hypoglycemia seen before the study. We note that Lexicon is developing its SGLT-2/SGLT-1 inhibitor, LX4211, for type 1 diabetes, though very little has been shared at this time.
SGLT-2 inhibitors would have a few key advantages for type 1 diabetes: 1) they come in pill form and are taken once per day; 2) no finely tuned titration or dosing is really needed, since the pill works in a glycemic dependent fashion (as glucose goes higher, the drug causes you to excrete more glucose through the urine; the reverse is true as glucose declines); and 3) there is a very low risk of hypoglycemia (except from insulin; protocol assumes insulin dosing is scaled back appropriately). There is generally some increased risk of urinary tract and genital infections, though these are usually successfully treated and caused few participants to leave clinical trials – many experts believe these are not a major concern and we certainly believe they should be more manageable than many other side effects like weight gain, nausea, etc. As more studies report results in type 1 diabetes, a clearer view of the drug's effects and optimal usage will emerge. Currently, two SGLT-2 inhibitors are on the market for type 2 diabetes: J&J Janssen's Invokana (canagliflozin) in the US and BMS/ AZ's Forxiga in Europe (we expect US approval at the end of 2013 or early 2014).
Striking Improvements in Hypoglycemia with the Medtronic MiniMed 530G/ Veo
On the technology side of ADA, there were two major studies that examined the Medtronic Veo with low glucose suspend. In the US, the pump is called the MiniMed 530G and is still under FDA review (the latest timeline calls for approval before the end of 2013). As a reminder, this first step toward the artificial pancreas includes a "threshold suspend" feature. This technology automatically suspends insulin delivery for two hours after a set low blood glucose threshold (e.g., 60 mg/dl) is reached on the CGM and the user does not respond to alarms. The pump has the most utility at night, when people often do not wake up to alarms and consequently, cannot treat their low blood glucose.
Dr. Trang Ly (Princess Margaret Hospital, Perth, Australia) presented results from a six- month study that compared using the Veo pump (with CGM, with low glucose suspend) to a pump alone (no CGM, no low glucose suspend) in people who are hypoglycemia unaware. In the six-month study, those using the Veo with low glucose suspend decreased their number of severe hypoglycemic events (seizure or coma) from six to zero, while those in the pump-only group saw an increase from five to six events. Additionally, participants using the Veo spent less time at blood glucose levels less than 70 mg/dl. These benefits came without any increase in their A1c. Diabetes technology expert Dr. Hans DeVries (University of Amsterdam, Netherlands) was very impressed with the results: "This is the most important study presented at this whole meeting."
In addition, Dr. Richard Bergenstal presented the much-awaited Automation to Simulate Pancreatic Insulin Response (ASPIRE) trial, which used the MiniMed 530G. In ASPIRE, half the participants used the MiniMed 530G with low glucose suspend while the remaining half used a typical CGM and insulin pump system (no automated suspension). The low glucose suspend group experienced a 32% reduction in nocturnal hypoglycemia events and a 38% reduction in the severity and duration of those events. Better still, there was no severe nocturnal hypoglycemia in the group using the Medtronic 530G, compared to four events in the control group. Even with the benefits on hypoglycemia, A1c did not change in those using the MiniMed 530G. When insulin delivery resumed after the two- hour suspension, the average blood glucose was about 93 mg/dl, rising to a modest 160 mg/dl two hours after the pump restarted. Dr. Bergenstal pointed out that temporarily going to 160 mg/dl is a small price to pay for no severe hypoglycemia. We agree.
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Most of the time, we bash the lastest news about a "diabetes cure" because it is neither a cure, nor often even a significant improvement in diabetes treatment. Usually these "cures" are tested in mice, but fail to make the leap over to human physiology. Devices may work in the lab, but take decades to pass through FDA review, and still not be much better than what we already have. It's enough to make us all jaded. I know I am. But I saw something...